Population studies of assisted reproductive technology and congenital anomalies in cerebral palsy

BACKGROUND: Risk factors for cerebral palsy (CP) have been identified across the conception, pregnancy, perinatal and postneonatal periods, including Assisted Reproductive Technology (ART) and congenital anomalies. ART likely increases risk of CP through mediating factors including multiple and preterm birth, but this requires further investigation in Australia. While congenital anomalies are an identified risk factor for CP, their reported prevalence varies widely. This thesis describes the epidemiology of CP with respect to these two independent factors. METHODS: A series of population-based studies were conducted. The influence of ART on prevalence of CP and clinical outcomes in Western Australia was explored in a population-based data-linkage study. Population-based research describing congenital anomalies in CP was synthesised in a systematic literature review. The most common congenital anomaly in CP from the review, congenital microcephaly, was investigated in a Western Australian population case-control study. Finally, population data-linkages were conducted in Australia and Europe to examine major congenital anomalies and outcomes in children with pre/perinatally acquired CP and postneonatally acquired CP (PNN-CP). RESULTS: ART was associated with a two-fold increased risk of CP. While multiple and preterm births were common after ART, additional risk of CP existed for very preterm ART singletons. The systematic review identified congenital anomalies in 12–32% of children with pre/perinatal CP and 20% of PNN-CP. Children with CP had a three-fold risk of congenital microcephaly in the case-control study. In Australia and Europe, congenital anomalies were identified in approximately one in four children with CP. Isolated cerebral anomalies were most common in children with pre/perinatally acquired CP, and isolated cardiac anomalies in PNN-CP. Congenital anomalies were associated with more severe outcomes for children with pre/perinatally acquired CP, but not PNN-CP. CONCLUSION: ART and congenital anomalies are important factors in the epidemiology of CP, and opportunities for prevention may lie in these pathways to CP. Research is planned to: a) evaluate temporal trends in ART and CP in Australia and b) further elucidate pathways and risk of CP for children with specific anomalies